Pharmacokinetics-pharmacodynamics and tissue distribution analysis of Low Polar extract of Xiaoyao Powder combined with rat model of chronic unpredictable mild stress

Abstract

Xiaoyao powder (XYP) is a valuable traditional Chinese Medicine (TCM) prescription developed for depression. Previous findings have suggested that the low polar extract of XYP (XYP-A) was more effect than other parts and its main ingredients included ligustilide, (2Z,8Z,10E)-pentadecatriene-4,6-diyn-1-ol (RB-1), (2Z,8E,10E)-pentadecatriene-4,6-diyn-1-ol (RB-2), (2Z,8Z,10E)-heptadecatriene-4,6-diyn-1-ol (RB-3), and bupleurynol (RB-4). However, the correlation between concentration of main ingredients and effects is still indeterminate. This study developed an ultra performance lipid chromatography combined with photo-diode array detector (UPLC-PDA) method to determine the contents of main ingredients in serum and tissues for pharmacokinetics and tissue distribution analysis. And, norepinephrine (NE) and 5-hydroxytryptamine (5-HT) were selected as the pharmacodynamic index and determined using the method of high performance lipid chromatography combined with fluorescence detector (HPLC-FD) in the serum for pharmacodynamics analysis. The DAS3.0 software was used to fit the pharmacokinetics-pharmacodynamics (PK-PD) model. The pharmacokinetic assay revealed that the absorption of polyacetylene compound was more favorable under pathological status. And, the result of tissue distribution showed that RB-2 and RB-4 were rapidly and widely distributed in tissues, and easy to cross the blood-brain barrier. The comparison of the value of NE and 5-HT in chronic unpredictable mild stress (CUMS) and control group rats suggested that 5-HT might be the main targets for the four polyacetylene compounds. The present study demonstrated that XYP-A showed the certain therapeutic effect of for depression safely and that polyacetylene compounds might be active ingredient for depression.